Polymer-immobilized α-iminoester

ABSTRACT

As an α-iminoester derivative that is stable under normal conditions and a method of producing various α-aminoester derivatives using them, a polymer-immobilized α-iminoester derivative represented by the following general formula (1): 
                 
 
wherein R 1  represents an alkyl chain of 1 or more carbons, and R 2  represents a hydrogen atom, halogen atom, or an alkyl group, aryl group or alkoxy group that may contain substituents, and a method of producing an α-iminoester derivative using them are provided.

TECHNICAL FIELD

The invention of the present application relates to apolymer-immobilized α-iminoester. More specifically, the invention ofthe present application relates to a method of producing an α-aminoesterderivative by using a polymer-immobilized α-iminoester.

BACKGROUND ART

The total synthesis of natural materials has become an important subjectin various fields such as medicine, agricultural chemicals and perfumes.α-iminoesters are extremely useful as precursors of nitrogen-containingnatural compounds such as α-amino acids (J. Am. Chem. Soc., 1989, 111,2582-2855; J. Org. Chem., 1988, 53, 1298-1307; J. Org. Chem., 1991, 56,1894-1901) and β-amino alcohols (J. Org. Chem., 1976, 41, 3121-3124; J.Am. Chem. Soc., 1997, 119, 7871-7872), and have attracted muchattention. However, the monomer tends to decompose or polymerize at roomtemperature and is extremely unstable and difficult to handle. For thesereasons, α-amino acids had to be prepared just before use, makingfurther progress in their use and development difficult.

The present inventors have previously reported the immobilization ofunstable silyl enole ethers on resins and their use in variouscarbon-carbon bond forming reactions (Tetrahedron Lett., 1996, 37,2809-2812; Tetrahedron Lett., 1996, 37, 5569-5572; Tetrahedron Lett.,1996, 37, 7783-7736; Tetrahedron Lett., 1997, 38, 4251-4254; MoleculesOnline, 1998, 2, 35-39; J. Org. Chem. 1998, 63, 4868-4869). If anα-iminoester could be immobilized on a polymer in the same manner, thecompound maybe stabilized and its handling and storage may be madeeasier. However, because α-iminoesters are unstable on their own, asdescribed above, it was difficult to even introduce them to a polymer.

The invention of the present application has been accomplished in viewof the aforementioned situations and its object is to provideα-iminoester derivatives that are stable under ordinary conditions andprovide a method of synthesizing various α-aminoester derivatives athigh yield using them, thereby overcoming the limitations of the priorart.

DISCLOSURE OF THE INVENTION

In order to accomplish the above-described objects, the invention of thepresent application firstly provides a polymer-immobilized α-iminoesterrepresented by the following general formula (1):

(wherein R¹ represents an alkyl chain of more than 1 carbon atom(s), andR² represents a hydrogen atom, halogen atom, or an alkyl group, arylgroup or alkoxy group that may contain substituents.)

Further, the invention of the present application secondly provides amethod of manufacturing an α-aminoester derivative, comprising the useof the above-described polymer-immobilized α-iminoester.

BEST MODE FOR CARRYING OUT THE INVENTION

As described above, the invention of the present application comprisesthe immobilization of an unstable α-iminoester on to a polymer, andhereinafter, the best mode for practicing the invention is described indetail.

The polymer-immobilized α-iminoester represented by the general formula(1) may be obtained by, for example, the hydrolysis of commerciallyavailable ethyldiethoxy acetate, followed by reaction with achloromethylated resin and treatment of the resulting diethoxy acetateresin with a hydrochloric acid/dioxane solution, after which the activeintermediate is reacted with an amine.

In this process, R¹ of general formula (1) is an alkyl chain of 1 ormore carbon atoms. The length of the alkyl chain may vary depending onthe alkyl chain bonded to the phenyl group at the terminus of the resin(although said alkyl chain may also be omitted). Further, a hydrogenatom may be attached to the resin terminus instead of an alkyl chain, inwhich case, R¹ becomes CH₂ by the chloromethylation of the resinterminus. Preferably, R¹ is an alkyl chain of 1 to 3 carbon atoms.

Further, in the above-described case, R² differs depending on the aminethat is to be reacted; for example, an alkyl group such as methyl,ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, hexyl, cyclohexyl,cyclobutyl or cyclopentyl, an alkylene group such as ethylene,propylene, butylene or amylene, or an aryl group such as phenyl, toluylor xylyl may be applied. Further, these substituents may further containsubstituents. For example, halogenated phenyl group, benzyl group,o-methylphenyl group or p-methoxyphenyl group maybe considered.Preferable examples are p-methoxyphenyl, p-halogenated pheny; of course,R² is not restricted to these and may be selected according to thedesired α-aminoester derivative.

In the invention of the present application, α-amino acids can beobtained at high stereoselectivity and yield, by using the novelpolymer-immobilized α-iminoester of the present invention as a startingmaterial and reacting it with a nucleophile. Further,tetrahydroquinoline derivatives can be obtained at a high yield byreacting the above novel substance with various alkenes. Moreover, solidphase aza Diels-Alder reaction can be performed smoothly using thepolymer-immobilized α-iminoester of the present invention.

The structure of the nucleophile and the reactants such as alkenes arenot particularly limited, and may be selected according to the desiredα-aminoester derivative species. Further, reaction conditions such assolvent, temperature and time, are not restricted either.

The invention of the present application is described more specificallyby the following Examples. It should be noted that the present inventionis not restricted to these Examples.

EXAMPLE Reference Example 1 Synthesis of Polymer-Immobilizedα-Iminoester

A diacetoxy acetate resin was synthesized according to chemical formula[A]. All products obtained after each step of the solid phase reactionwere monitored by Swollen-Resin Magic Angle Spinning NMR (SR-MAS NMR).

(1) Synthesis of Diethoxyacetate Resin (Compound 2)

To a suspension of chloromethyl copoly-(styrene-1%-divinyl benzene)resin (1.24 mmol/g, 10.0 g, 12.4 mmol) in DMF (100 ml), was added sodiumdiethoxyacetate (3.0 eq., 6.37 g, 37.2 mmol) and tetra-n-butyl ammoniumiodide (1.0 eq., 4.58 g, 12.4 mmol), and stirred under inert atmospherefor 12 hours at 60° C. After the reaction solution was filtered andwashed with water, THF and dichloromethane, a diethoxyacetate resin(Compound 2, 1.09 mmol/g) was obtained. The loading of Compound (2) wasdetermined by chlorine titration (Volhard's method). The result ofidentification was as shown in Table 1.

TABLE 1 Compound (2) ¹³C SR-MAS NMR (CDCl₃) δ = 15.0, 40.3, 62.3, 66.7,97.3, 125.6, 127.9, 145.3, 167.4 IR (KBr) 1755 cm⁻¹(2) Synthesis of 2-Chloro-2-Ethoxyacetate Resin (Compound 3)

To a suspension of compound (2) (1.09 mmol/g, 10.0 g, 10.9 mmol) in 4Nhydrogenchloride dioxane solution (100 ml) was added acetyl chloride(5.0 eq., 3.9 ml, 54.5 mmol) and stirred at room temperature for 12hours. After the reaction solution was filtered and washed with THF anddichloromethane, a 2-chloro-2-ethoxyacetate resin (Compound 3, yield99%, 1.10 mmol/g) was obtained. The loading of Compound (2) wasdetermined by chlorine titration (Volhard's method). The result ofidentification is shown in Table 2.

TABLE 2 Compound (3) NMR (CDCl₃) δ = 14.2, 40.3, 66.3, 67.7, 88.4,125.6, 127.9, 145.3, 161.1 IR (KBr) 1760 cm⁻¹(3) Synthesis of 2-(4′-Methoxyphenyl)Iminoacetate Resin (Compound 5)

To a suspension of compound (3) (1.10 mmol/g, 181.8 mg, 0.2 mmol) in DMF(100 ml) was added p-anisidine (Compound 4a) (5.0 eq., 123.2 mg, 1.0mmol) and stirred at room temperature for 12 hours. After the reactionsolution was filtered and washed with THF and dichloromethane, a2-(4′-methoxyphenyl) iminoacetate resin (Compound 5a, 1.10 mmol/g) wasobtained. The result of identification was as shown in Table 3.

TABLE 3 Compound (5a) NMR (CDCl₃) δ = 40.3, 55.4, 67.2, 114.5, 123.6,125.6. 127.9, 141.3, 147.5 160.5, 163.2 IR (KBr) 1760 cm⁻¹(4) Conversion to 2-(4′-methoxyphenyl)Aminoethanol (Compound 6a)

In order to determine the loading of the above-described Compound (5a),2-(4′-methoxyphenyl)iminoacetate resin was transformed in to2-(4′-methoxyphenyl) aminoethanol (Compound 6a) by the followingprocedure.

Compound (5a) and lithium borane (5.0 eq., 21.8 mg, 1.0 mmol) were addedto THF (5 ml) and stirred at room temperature for 12 hours. An aqueous1N HCl solution was added to the reaction solution to terminatereaction, after which saturated sodium hydrogen carbonate was added. Theaqueous layer was extracted with dichloromethane and the organic layerwas dried over sodium sulfate. After removing the solvent, the crudeproduct was purified by TLC to obtain 2-(4′-methoxyphenyl)aminoethanol(Compound 6a, 33.4 mg). The result of identification is shown below.

TABLE 4 Compound (6a) ¹HNMR(CDCl₃) δ = 2.71(brs.2H), 3.25(t, 2H.J =5.2Hz), 3.75(s, 3H), 3.81(t, 2H, J = 5.2Hz), 6.63(d, 2H, J = 9.0Hz),6.79(d, 2H, J = 9.0Hz): ¹³CNMR(CDCl₃) δ=4 7.2, 55.8, 61.3, 114.5, 114.9,142.2, 152.5: MS(EI)m/z = 167 IR(KBr)1760cm⁻¹

Accordingly, identification results for 2-(4′-chlorophenyl) aminoethanol(6b) obtained by the above steps (3)-(4) using Compound 4b as the amine,and 2-(4′-bromophenyl)aminoethanol (6c) obtained by the above steps(3)-(4) using 4c as the amine, are shown in Table 5 and Table 6,respectively.

TABLE 5

Compound (6b) ¹H NMR (CDCl₃) δ = 2.69 (brs. 2H), 3.19 (t, 2H. J = 5.1Hz), 3.75 (t, 2H, J = 5.2 Hz), 6.50 (d, 2H, J = 8.9 Hz), 7.05 (d, 2H, J= 8.9 Hz): ¹³C NMR (CDCl₃) δ = 46.2. 61.1. 114.9, 122.5, 129.1, 146.6:MS (EI) m/z = 171

TABLE 6 Compound (6c) ¹HNMR(CDCl₃) δ = 2.73(brs.2H), 3.20(t, 2H.J =5.1Hz), 3.76(t, 2H, J = 5.1Hz), 6.47(d, 2H, J = 8.8Hz), 7.19(d, 2H, J =8.9Hz): ¹³CNMR(CDCl₃) δ =46.1, 61.1, 109.6, 114.8, 132.0, 146.9:MS(EI)m/z = 215

Example 1 Mannich-Type Reaction Using Polymer-Immobilized α-Iminoester

A γ-oxo-α-amino acid derivative was synthesized by the Mannich-typereaction using the polymer-immobilized α-iminoester of the presentinvention as the starting material in accordance with chemical formula[B]

To a suspension of Sc(OTf)₃ (20 mol %, 19.7 mg, 0.04 mmol) and theCompound (5a) (1.10 mmol/g, 181.8 mg. 0.2 mmol) indichloromethane-acetonitrile (1:1, 3 ml),1-methoxy-2-methyl-1-trimethylsiloxy-1-propene (Compound 7a, 5.0 eq.,174.3 mg, 1.0 mmol) in dichloromethane-acetonitrile (1:1, 1 ml) wasadded, and the mixture was stirred at room temperature for 20 hours.

After saturated aqueous sodium hydrogen carbonate was added to quenchthe reaction, the polymer was filtered and washed with water, THF anddichloromethane, and dried.

The resultant polymer was combined with sodium methoxide (2.0 eq., 1M)in THF-methanol (1:1, 4 ml) and stirred for 1 hour at room temperature.After adding 4N HCl dioxane solution (0.1 ml), the reaction solution wasfiltered and the solvents were removed from the filtrate under a reducedpressure. The crude product was purified by preparative TLC to afforddimethyl 3,3-dimethyl-2-(4′-methoxyphenyl)aminosuccinate (8a, 44.9 mg,yield 76%).

The identification result is shown below.

TABLE 7 Compound (8a) ¹HNMR(CDCl₃) δ = 1.24(s, 3H), 1.28(s, 3H), 3.65(s,3H), 3.69(s, 3H), 3.71(s, 3H), 4.23(s, 1H), 6.67(d, 1H, J = 8.8Hz),6.74(d, 2H, J = 8.8Hz): ¹³CNMR(CDCl₃) δ = 21.6, 22.5, 46.1, 52.0, 52.2,55.7, 64.9, 114.8, 116.1, 141.2, 153.2, 172.7, 176.1: IR(neat)1512,1737, 3378cm⁻¹ MS(EI)m/z = 295

Further, identification results for the products (Compound 8b-8c)obtained by the Mannich reaction of Compound (5a) with variousnucleophiles (Compounds 7b-7e) other than1-methyxo-2-methyl-1-polymethyl siloxy-1-propene (Compound 7a) shown inTable 8 are indicated in Tables 8 to 12. Particularly, whenDanishefsky's diene (J. Am. Chem. Soc., 1974, 96, 7807-7809; TetrahedronLett., 1982, 23, 3739-3742) was used as a nucleophile,2-methoxycarbonyl-1-(4′-methoxyphenyl)-1,2,3,4-tetrahydrop yridin-2-on(Compound 8e) was obtained in 69% yield.

TABLE 8 (8a-d)

Yield Nucleophile Product (%)^(a)

76

94^(b)

71^(c)

65^(c,d)

69³ ^(a)Based on (5a), ^(b)Diastereomer ratio = 60:40, ^(c)Sc(OTf)3 (40mol %) used, ^(d)Diastereomer ratio not determined, ^(e)Reaction at −5°C.

TABLE 9 Compound (8b) (major):¹HNMR(CDCl₃) δ = 3.50(s, 3H), 3.64(s,3.H), 3.68(s, 3H), 4.37(d, 1H, J= 11.9Hz), 4.41-4.53(m.2H), 4.61 (s,1H), 4.83(d, 1H, J = 11.9Hz), 6.54(d, 2H, J = 8.8Hz), 6.66 (d, 2H, J =8.8Hz), 7.16-7.35(m, 5H):¹³CNMR(CDCl₃) δ = 52.3, 52.4, 53.6, 60.8, 65.3,73.0, 114.6, 116.1, 128.1, 128.2, 128.4, 136.7, 140.6, 153.2, 170.2,171.1:(minor): ¹HNMR(CDCl₃) δ = 3.658(s, 3H), 3.661(s, 3H), 3.73(s, 3H),4.27(d, 1H, J = 3.7 Hz), 4.37(d, 1H,J = 11.7Hz), 4.47)(d, 1H, J =3.7Hz), 4.62(s, 1H), 4.76(d, 1H, J = 11.7Hz), 6.52(d, 2H, J = 8.8Hz),6.68(d, 2H, J = 8.8Hz), 7.20-7.35(m, 5H):¹³C NMR(CDCl₃) δ = 52.3, 52.5,55.6, 60.3, 73.2, 77.7, 114.9, 115.7, 127.9, 128.0, 128.4, 136.8, 139.4,153.1, 170.3, 170.5:IR(neat)1514, 1752, 3371cm⁻¹:MS(EI)m/z = 373.

TABLE 10 Compound (8c) ¹HNMR(CDCl₃) δ = 3.47(d, 2H, J = 3.4Hz), 3.65(s,3H), 3.66(s, 3H), 4.48(t, 1H, J = 5.4Hz). 6.60(d, 2H, J = 8.9Hz),6.70(d, 2H, J = 8.9Hz). 7.35 -7.55(m, 3H), 7.80-7.90(m, 2H):¹³CNMR(CDCl₃) δ = 41.1, 52.4, 54.2, 55.6, 114.8, 115.6, 128.1, 128.7,133.5, 136.3, 140.4, 153.0, 173.7, 197.3:IR(neat)1513, 1632, 1729,3365cm⁻¹:MS(EI)m/z = 313.

TABLE 11 Compound (8d) ¹HNMR(CDCl₃) δ= 1.22-1.36(m, 3H), 3.58-3.65(m,3H), 3.67-3.74(m, 3H), 3.92-4.06 (m, 1H), 4.32-4.41(m, 1H), 6.49-6.77(m,4H), 7.36-7.61 (m, 3H), 7.87(d, 2H, J=7.3 Hz):¹³CNMR(CDCl₁) δ = 13.6,14.8, 43.2, 43.8, 52.0, 52.2, 55.6, 60.2, 61.0, 114.7, 115.6, 115.8,128.28, 128.30, 128.70, 128.73, 133.21, 133.29, 135.9, 136.4, 140.6,140.9, 152.9, 153.0, 173.4, 173.3, 201.3, 201.8:IR(neat)1514, 1682,1736, 3389cm⁻¹: MS(EI)m/z = 261.

TABLE 12 Compound (8e) ¹HNMR(CDCl₃) δ = 2.90(dq, 1H, J=1.1, 16.8Hz),3.05(dd, 1H, J = 7.5, 16.8 Hz), 3.739(s, 3H), 3.78(s, 3H), 4.67(dd, 1H,J = 1.1, 7.5Hz), 5.18(d, 1H, J = 7.7Hz), 6.88(d, 2H, J = 9.0Hz), 7.06(d,2H, J = 9.0Hz), 7.38(dd, 1H, J = 1.1, 7.7Hz):¹³C NMR(CDCl₃) δ = 38.3,53.0, 55.5, 61.1, 101.8, 114.7, 121.8, 138.1, 150.0, 157.3, 170.3,189.0:IR(neat)1509, 1581, 1652, 1743cm⁻¹:MS(EI)m/z = 327.

Example 2 Synthesis of Tetrahydroquinoline Derivatives UsingPolymer-Immobilized α-Iminoester

Tetrahydroquinoline derivatives were synthesized according to thereaction of chemical formula [C].

To a suspension of Sc(OTf)₃ (20 mol %, 19.7 mg, 0.04 mmol) and Compound(5a) (1.10 mmol/g, 181.8 mg, 0.2 mmol) in dichloromethane-acetonitrile(1:1, 3 ml), a solution of 2,3-dihydropropane (Compound 9a, 5.0 eq.,70.1 mg, 1.0 mg, 1.0 mmol) in dichloromethane-acetonitrile (1:1, 1 ml)was added and stirred at room temperature for 20 hours.

After the addition of saturated aqueous sodium hydrogen carbonate toquench the reaction, the resin was filtered and washed with water, THFand dichloromethane, and dried.

The resulting polymer and sodium methoxide (2.0 eq., 1M) were added toTHF-methanol (1:1, 4 ml) and stirred at room temperature for one hour.After adding 4N HCl dioxane solution (0.1 ml), the reaction solution wasfiltered and the solvent was removed under a reduced pressure. The crudeproduct was purified by preparative TLC to obtain8-methoxy-4-methoxycarbonyl-2,3,3a,4,5,9b-hexahydrofurano [C]-quinoline(Compound 10a, 37.9 mg, yield 72%).

The identification result is shown in Table 13.

TABLE 13 Compound (10a) ¹HNMR(CDCl₃)δ = 1.82-1.92(m, 1H), 1.95-2.06(m,1H), 3.07(dq, 1H, J=3.2, 8.6Hz), 3.65-3.90(m, 7H), 4.44(d, 1H, J=3.2Hz),5.15(d, 1H, J=8.6Hz), 6.56(d, 1H, J=8.6Hz), 6.69(dd, 1H, J=2.8, 8.6Hz),6.84(d, 1H, J=2.8Hz): ¹³CNMR(CDCl₃)δ = 25.2, 40.3, 52.4, 55.7, 55.8,66.6, 75.8, 113.6, 115.9, 116.2, 123.1, 137.3, 153.2, 171.8; (minor):¹³HNMR(CDCl₃)δ = 2.10-2.33(m, 2H), 2.60-2.69(m, 1H), 3.58(d, 1H,J=9.5Hz), 3.74(s, 3H), 3.77-3.85(m, 4H), 3.92-4.00(m, 1H), 4.62(d, 1H,J=6.3Hz), 6.63 (d, 1H, J=8.8Hz), 6.73(dd, 1H, J=2.9, 8.8Hz), 6.89(d, 1H,J=2.9Hz): ¹³CNMR(CDCl₃)δ = 29.6, 39.3, 52.4, 55.7, 56.2, 65.8, 75.1,113.9, 116.5, 116.6, 121.4, 136.9, 153.0, 172.8: IR(neat) 1622, 1737,3367cm⁻¹.

Further, the same reaction was conducted using Compounds (5a)-(5c) asthe starting material and Compounds (9a)-(9d) as the alkene. Theresulting products, as well as their yield and selectivity are shown inthe following table.

TABLE 14 Materials Tetrahydroquinoline Derivatives Yield Selectivity5a + 9a

72%^(a) 68/32 5b + 9a

84%^(a) 60/32 5b + 9b

78%^(a) 75/25 5c + 9b

quant^(a) 68/32 5b + 9c

95%^(a) 95/5  5c + 9d

quant^(a) 93/7  ^(a)Based on 5d

The identification results for Compounds (10b)-(10f) are shown in thefollowing Tables 15-19,

TABLE 15 Compound (10b) (major): ¹HNMR(CDCl₃)δ = 1.97-2.29(m, 2H),2.53-2.60(m, 1H), 3.57(d, 1H, J=9.0Hz), 3.70-3.83(m, 4H), 3.89(dd, 1H,J=5.4, 8.4Hz), 4.53(d, 1H, J=6.1Hz), 6.54(d, 1H, J=8.7Hz), 6.99(dd, 1H,J=2.4, 8.7Hz), 7.23(d, 1H, J=2.4Hz): ¹³CNMR(CDCl₃)δ = 29.4, 38.8, 52.6,55.3, 65.6, 116.2, 121.7, 123.5, 128.9, 130.1, 141.6, 172.5: (minor):¹HNMR(CDCl₃)δ = 1.70-2.00(m, 2H), 2.95-3.10(m, 1H), 3.65-3.80(m, 5H),4.14(d, 1H, J=3.1Hz), 5.07(d, 1H, J=7.9Hz), 6.47(d, 1H, J=8.6 HZ),6.95(dd, 1H, J=2.3, 8.6Hz), 7.20(d, 1H, J=2.3Hz): ¹³CNMR(CDCl₃)δ = 25.0,39.9, 52.6, 54.9, 66.6, 115.9, 123.4, 123.8, 128.6, 129.5, 141.7, 172,5:IR (neat)1649, 1739cm⁻¹: MS(EI)m/z=267.

TABLE 16 Compound (10c) (major): ¹HNMR(CDCl₃)δ = 1.64(s, 3H), 2.15(dd,1HJ=4.1, 13.4Hz), 2.24(dd, 1H, J=10.1, 13.4Hz), 3.53(s, 3H), 4.10(dd,1H, J=4.1, 10.1Hz), 6.53(d, 1H, J=8.5Hz), 6.60(d, 1H, J=2.4Hz), 6.90(dd, 1H, J=2.4, 8.5Hz), 7.11-7.25(m, 5H): ¹³CNMR(CDCl₃)δ = 28.7, 41.20,41.23, 51.4, 52.3, 115.9, 122.2, 126.4, 127.2, 127.3, 128.1, 128.6,130.3, 141.2, 148.0, 173.2: (minor): ¹HNMR(CDCl₃)δ = 1.67(s, 3H),1.87(dd, 1HJ=12.3, 12.9Hz), 2.43(dd, 1H, J=3.5, 12.9Hz), 3.52(dd, 1H,J=3.5, (2.3Hz), 3.66(s, 3H), 6.33(d, 1H, J=9.0Hz), 6.95-7.32(m, 5H):¹³CNMR(CDCl₃)δ = 29.0, 40.1, 41.1, 50.8, 52.4, 114.6, 115.6, 126.3,126.9, 127.4, 127.6, 128.4, 129.1, 141.5, 147.9, 173.4: IR(neat)1713,3384cm⁻¹: MS(EI)m/z=315.

TABLE 17 Compound (10d) (major): ¹HNMR(CDCl₃)δ = 1.71(s, 3H), 2.21(dd,1HJ=4.1, 13.3Hz), 2.30(dd, 1H, J=10.1, 13.3Hz), 3.59(s, 3H), 4.16(dd,1H, J=4.1, 10.1Hz), 6.54(d, 1H, J=8.6Hz), 6.80(d, 1H, J=2.1Hz), 7.10(dd, 1H, J=2.1, 8.6Hz), 7.15-7.40(m, 5H): ¹³CNMR(CDCl₃)δ = 28.7, 41.2,51.4, 52.3, 100.5, 109.3, 116.3, 126.4, 127.3, 128.2, 128.9, 130.0,130.7, 131.45, 131.51, 132.2, 141.6, 147.9, 173.1: (minor):¹HNMR(CDCl₃)δ = 1.75(s, 3H), 1.94(dd, 1HJ=12.2, 12.8Hz), 2.50(dd, 1H,J=3.4, 12.8Hz), 3.59(dd, 1H, J=3.4, 12.8Hz), 3.73(s, 3H), 6.55(d, 1H,J=8.6Hz), 7.06(d, 2H, J=7.2Hz), 7.18(dd, 1H, J=2.0, 6.4Hz), 7.30-7.43(m,3H): ¹³CNMR(CDCl₃)δ = 29.0, 40.1, 41.1, 50.8, 52.4, 109.1, 116.0, 126.3,126.9, 128.2, 128.4, 130.2, 130.5, 141.9, 147.9, 173.4: IR(neat)1713,3408cm⁻¹: MS(EI)m/z=359.

TABLE 18 Compound (10e) ¹HNMR(CDCl₃)δ = 2.68(dd, 1H, J=8.0, 15.4Hz),3.02(dd, 1H, J=10.2, 15.4Hz), 3.29-3.39(m, 1H), 3.71(s, 3H), 4.10,(d,1H, J=3.2Hz), 4.33(d, 1H, J=8.3Hz), 6.42(d, 1H, J=8.6Hz), 6.80(dd, 1H,J=2.2, 8.6Hz), 7.00-7.15(m, 3H): ¹³CNMR(CDCl₃)δ = 31.6, 42.3, 45.5,52.3, 116.5, 123.2, 124.8, 124.9, 125.1, 126.7, 126.8, 127.3, 128.7,141.8, 142.1, 144.9, 171.9: IR(neat)1713, 3409cm⁻¹: MS(EI)m/z=313.

TABLE 19 Compound (10f) ¹HNMR(CDCl₃)δ = 1.75(s, 3H), 2.58-2.70(m, 1H),2.90-3.02(m, 2H), 3.85(s, 3H), 4.31(d, 1H, J=2.4Hz)6.45(d, 1H, J=8.8Hz),6.99(dd, 1H, J=2.4, 8.8Hz), 7.080-7.30(m, 4H), 7.48(d, 1H, J=7.2Hz):¹³CNMR(CDCl₃)δ = 29.6, 30.6, 48.1, 49.7, 52.1, 52.5, 110.0, 116.6,123.4, 124.8, 126.8, 127.2, 128.8, 129.7, 131.5, 140.7, 141.0, 148.7,172.4: IR(neat)1712, 3409cm⁻¹: MS(EI)m/z=371.

In each of the reactions, the solid phase reaction proceeded smoothlyand tetrahydroquinoline derivatives corresponding to each startingmaterial and reactant were obtained at high yield. Further, it was shownthat even halogenated compounds were stable in these reactions.

INDUSTRIAL APPLICABILITY

As has been described above in detail, a new polymer-immobilizedα-iminoester has been provided by the invention of the presentapplication. Using this polymer-immobilized α-iminoester, α-aminoesterderivatives, which are known to be important in the field ofbiochemistry, can be synthesized in high yield.

1. A polymer-immobilized α-iminoester, which is represented by thefollowing formula (1):

wherein R¹ represents an alkyl chain of 1 or more carbon atom(s), and R²represents a hydrogen atom, halogen atom, alkyl group, alkylene group,p-substituted phenyl group or alkoxy group, wherein

wherein the polymer is a copoly (styrene-divinyl benzene) resin.
 2. Amethod of producing an α-aminoester, which comprises reacting thepolymer-immobilized α-iminoester of the following formula (1):

wherein R¹ represents an alkyl chain of 1 or more carbon atom(s), and R²represents a hydrogen atom, halogen atom, alkyl group, alkylene group,p-substituted phenyl group or alkoxy group, wherein

wherein the polymer is a copoly (styrene-divinyl benzene) resin, with anucleophile.
 3. The polymer-immobilized α-iminoester of claim 1 whereinR¹ is an alkyl chain of 1 to 3 carbon atoms.
 4. The polymer-immobilizedα-iminoester of claim 1 wherein R² is p-halogenated phenyl orp-methoxyphenyl.
 5. A method of producing a tetrahydroquinoline, whichcomprises reacting the polymer-immobilized α-iminoester of the followingformula (1):

wherein R¹ represents an alkyl chain of 1 or more carbon atom(s), and R²represents a hydrogen atom, halogen atom, alkyl group, alkylene group,p-substituted phenyl group or alkoxy group, wherein

wherein the polymer is a copoly (styrene-divinyl benzene) resin, with analkene.